GacS/GacA is a two component signal transduction system (“TCSTS”) that is widely distributed in many bacteria to respond to environmental stimuli and adapt to different environmental conditions. GacS is a putative histidine kinase sensor and GacA is the response regulator. The homologs of the TCSTS of GacS/GacA have been reported in a variety of Gram-negative bacteria, including E. coli (BarA/UvrY), Pectobacterium spp., S. typhimurium (BarA/SirA), Pseudomonas spp. (GacS/GacA), Legionella pneumophila (LetS/LetA) and Vibrio species.
GacS/GacA and homologous systems regulate many virulence factors including, but not limited to, regulatory RNA, quorum sensing (“QS”) signals, type III secretion system (“T3SS”) genes, pectate lyases, proteases, biofilm formation, and toxins. For example, in D. dadantii, the GacS/GacA system is located at the top of a regulatory cascade and functions as a central regulator by controlling an assortment of transcriptional and posttranscriptional factors. Mainly, the influence of the GacS/GacA system on pectinase production and T3SS gene expression is channeled through a regulatory RNA system, the Rsm system, by activating rsmB which binds to and inhibits the T3SS mRNA decay effect of RsmA.
In addition to the GacS/GacA-RsmA-rsmB-hrpL regulatory pathway, the T3SS of Dickeya dadantii, which belongs to Group I T3SS of phytobacteria, is regulated by a HrpX/Y-HrpS-HrpL pathway. The two-component system HrpX/HrpY activates the gene encoding HrpS, which is required for expression of hrpL. HrpL, an alternative sigma factor, further activates expression of genes encoding the T3SS apparatus and its secreted products. Thus, the GacS/GacA and HrpX/HrpY TCSTS systems both exert a regulatory effect in D. dadantii, in particular through the T3SS system.